S35A1_MOUSE
ID S35A1_MOUSE Reviewed; 336 AA.
AC Q61420; A2AT44;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=CMP-sialic acid transporter {ECO:0000303|PubMed:8755516};
DE Short=CMP-SA-Tr {ECO:0000303|PubMed:8755516};
DE Short=CMP-Sia-Tr;
DE Short=CST {ECO:0000303|PubMed:30985278};
DE AltName: Full=Solute carrier family 35 member A1;
GN Name=Slc35a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND TRANSPORTER ACTIVITY.
RX PubMed=8755516; DOI=10.1073/pnas.93.15.7572;
RA Eckhardt M., Muehlenhoff M., Bethe A., Gerardy-Schahn R.;
RT "Expression cloning of the Golgi CMP-sialic acid transporter.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:7572-7576(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, MEMBRANE TOPOLOGY, AND TRANSPORTER
RP ACTIVITY.
RX PubMed=10085119; DOI=10.1074/jbc.274.13.8779;
RA Eckhardt M., Gotza B., Gerardy-Schahn R.;
RT "Membrane topology of the mammalian CMP-sialic acid transporter.";
RL J. Biol. Chem. 274:8779-8787(1999).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, TRANSPORTER ACTIVITY, AND MUTAGENESIS OF MET-20; ALA-24; TYR-27;
RP ALA-105; GLN-118; TYR-121; GLN-122; ALA-184; ALA-253; GLY-256 AND THR-260.
RX PubMed=34015330; DOI=10.1016/j.jbc.2021.100789;
RA Ury B., Potelle S., Caligiore F., Whorton M.R., Bommer G.T.;
RT "The promiscuous binding pocket of SLC35A1 ensures redundant transport of
RT CDP-ribitol to the Golgi.";
RL J. Biol. Chem. 296:100789-100789(2021).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.58 ANGSTROMS) OF 1-322 IN COMPLEX WITH CMP-SIALIC
RP ACID, FUNCTION, TOPOLOGY, MUTAGENESIS OF 322-SER--VAL-336, TRANSPORTER
RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=30985278; DOI=10.7554/elife.45221;
RA Ahuja S., Whorton M.R.;
RT "Structural basis for mammalian nucleotide sugar transport.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: Transports CMP-sialic acid from the cytosol into Golgi
CC vesicles where glycosyltransferases function (PubMed:8755516,
CC PubMed:10085119, PubMed:30985278, PubMed:34015330). Efficient CMP-
CC sialic acid uptake depends on the presence of free CMP inside the
CC vesicles, suggesting the proteins functions as an antiporter
CC (PubMed:30985278). Binds both CMP-sialic acid and free CMP, but has
CC higher affinity for free CMP (PubMed:30985278). Also mediates the
CC transport of CDP-ribitol (PubMed:34015330).
CC {ECO:0000269|PubMed:10085119, ECO:0000269|PubMed:30985278,
CC ECO:0000269|PubMed:34015330, ECO:0000269|PubMed:8755516}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CMP(out) + CMP-N-acetyl-beta-neuraminate(in) = CMP(in) + CMP-
CC N-acetyl-beta-neuraminate(out); Xref=Rhea:RHEA:67724,
CC ChEBI:CHEBI:57812, ChEBI:CHEBI:60377;
CC Evidence={ECO:0000269|PubMed:10085119, ECO:0000269|PubMed:30985278,
CC ECO:0000269|PubMed:34015330, ECO:0000269|PubMed:8755516};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=CDP(out) + CDP-L-ribitol(in) = CDP(in) + CDP-L-ribitol(out);
CC Xref=Rhea:RHEA:71579, ChEBI:CHEBI:57608, ChEBI:CHEBI:58069;
CC Evidence={ECO:0000269|PubMed:34015330};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=13.2 uM for CMP-N-acetyl-beta-neuraminate
CC {ECO:0000269|PubMed:30985278};
CC Vmax=6.5 nmol/min/mol enzyme for CMP-N-acetyl-beta-neuraminate
CC {ECO:0000269|PubMed:30985278};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P78382}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:10085119, ECO:0000269|PubMed:8755516}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:10085119}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Found in all the tissues examined
CC including skeletal muscle, brain, heart, liver, kidney and spleen.
CC {ECO:0000269|PubMed:8755516}.
CC -!- SIMILARITY: Belongs to the nucleotide-sugar transporter family. SLC35A
CC subfamily. {ECO:0000305}.
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DR EMBL; Z71268; CAA95855.1; -; mRNA.
DR EMBL; AL928738; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012252; AAH12252.1; -; mRNA.
DR CCDS; CCDS18030.1; -.
DR RefSeq; NP_036025.2; NM_011895.3.
DR PDB; 6OH2; X-ray; 2.58 A; A=1-322.
DR PDB; 6OH3; X-ray; 2.75 A; A=1-322.
DR PDB; 6OH4; X-ray; 3.38 A; A/B=1-336.
DR PDB; 6XBO; X-ray; 1.80 A; A=1-322.
DR PDBsum; 6OH2; -.
DR PDBsum; 6OH3; -.
DR PDBsum; 6OH4; -.
DR PDBsum; 6XBO; -.
DR AlphaFoldDB; Q61420; -.
DR SMR; Q61420; -.
DR STRING; 10090.ENSMUSP00000029970; -.
DR TCDB; 2.A.7.12.1; the drug/metabolite transporter (dmt) superfamily.
DR iPTMnet; Q61420; -.
DR PhosphoSitePlus; Q61420; -.
DR EPD; Q61420; -.
DR MaxQB; Q61420; -.
DR PaxDb; Q61420; -.
DR PRIDE; Q61420; -.
DR ProteomicsDB; 260771; -.
DR Antibodypedia; 46448; 25 antibodies from 12 providers.
DR DNASU; 24060; -.
DR Ensembl; ENSMUST00000029970; ENSMUSP00000029970; ENSMUSG00000028293.
DR GeneID; 24060; -.
DR KEGG; mmu:24060; -.
DR UCSC; uc012dbo.1; mouse.
DR CTD; 10559; -.
DR MGI; MGI:1345622; Slc35a1.
DR VEuPathDB; HostDB:ENSMUSG00000028293; -.
DR eggNOG; KOG2234; Eukaryota.
DR GeneTree; ENSGT00950000182827; -.
DR HOGENOM; CLU_024645_1_0_1; -.
DR InParanoid; Q61420; -.
DR OMA; WKLKSIV; -.
DR OrthoDB; 703674at2759; -.
DR PhylomeDB; Q61420; -.
DR TreeFam; TF315345; -.
DR Reactome; R-MMU-4085001; Sialic acid metabolism.
DR Reactome; R-MMU-727802; Transport of nucleotide sugars.
DR BioGRID-ORCS; 24060; 27 hits in 78 CRISPR screens.
DR ChiTaRS; Slc35a1; mouse.
DR PRO; PR:Q61420; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q61420; protein.
DR Bgee; ENSMUSG00000028293; Expressed in conjunctival fornix and 252 other tissues.
DR ExpressionAtlas; Q61420; baseline and differential.
DR Genevisible; Q61420; MM.
DR GO; GO:0030173; C:integral component of Golgi membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0015297; F:antiporter activity; IDA:UniProtKB.
DR GO; GO:0005456; F:CMP-N-acetylneuraminate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0005459; F:UDP-galactose transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0015782; P:CMP-N-acetylneuraminate transmembrane transport; IDA:UniProtKB.
DR InterPro; IPR007271; Nuc_sug_transpt.
DR PANTHER; PTHR10231; PTHR10231; 1.
DR Pfam; PF04142; Nuc_sug_transp; 1.
DR PIRSF; PIRSF005799; UDP-gal_transpt; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Golgi apparatus; Membrane; Reference proteome;
KW Sugar transport; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..336
FT /note="CMP-sialic acid transporter"
FT /id="PRO_0000213352"
FT TOPO_DOM 1..9
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:10085119,
FT ECO:0000269|PubMed:30985278"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 31..45
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 46..64
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 65..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 109..114
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 115..135
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 136..141
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 142..160
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 161..175
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 197..209
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 210..228
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 229..243
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 244..262
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 263..269
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 270..288
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 289..296
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TRANSMEM 297..315
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:30985278"
FT TOPO_DOM 316..336
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:10085119,
FT ECO:0000269|PubMed:30985278"
FT REGION 316..336
FT /note="Disordered"
FT /evidence="ECO:0000269|PubMed:30985278"
FT BINDING 55
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000269|PubMed:30985278,
FT ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT BINDING 101..102
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000269|PubMed:30985278,
FT ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT BINDING 117..124
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000269|PubMed:30985278,
FT ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT BINDING 188
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000269|PubMed:30985278,
FT ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT BINDING 210..214
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000269|PubMed:30985278,
FT ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT BINDING 272
FT /ligand="CMP-N-acetyl-beta-neuraminate"
FT /ligand_id="ChEBI:CHEBI:57812"
FT /evidence="ECO:0000269|PubMed:30985278,
FT ECO:0007744|PDB:6OH2, ECO:0007744|PDB:6OH3"
FT MUTAGEN 20
FT /note="M->S: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 24
FT /note="A->Y: Loss of CMP-sialic acid transport activity but
FT no effect on CDP-ribitol transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 27
FT /note="Y->H: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 105
FT /note="A->V: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 118
FT /note="Q->A: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 121
FT /note="Y->S: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 122
FT /note="Q->A: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 184
FT /note="A->Y: Loss of CMP-sialic acid transport activity but
FT no effect on CDP-ribitol transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 253
FT /note="A->Q: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 256
FT /note="G->N: Loss of CMP-sialic acid transport activity but
FT no effect on CDP-ribitol transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 260
FT /note="T->M: No effect on CDP-ribitol and CMP-sialic acid
FT transport activity."
FT /evidence="ECO:0000269|PubMed:34015330"
FT MUTAGEN 322..336
FT /note="Missing: No effect on CMP-sialic acid transport
FT activity."
FT /evidence="ECO:0000269|PubMed:30985278"
FT CONFLICT 18
FT /note="T -> A (in Ref. 1; CAA95855 and 3; AAH12252)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="T -> S (in Ref. 1; CAA95855 and 3; AAH12252)"
FT /evidence="ECO:0000305"
FT HELIX 10..36
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 44..67
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 70..80
FT /evidence="ECO:0007829|PDB:6XBO"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 85..111
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 114..121
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 124..135
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 142..159
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 174..199
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 206..236
FT /evidence="ECO:0007829|PDB:6XBO"
FT TURN 238..241
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 244..266
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 269..291
FT /evidence="ECO:0007829|PDB:6XBO"
FT HELIX 297..313
FT /evidence="ECO:0007829|PDB:6XBO"
SQ SEQUENCE 336 AA; 36453 MW; A396528233904451 CRC64;
MAPARENVSL FFKLYCLTVM TLVAAAYTVA LRYTRTTAEE LYFSTTAVCI TEVIKLLISV
GLLAKETGSL GRFKASLSEN VLGSPKELAK LSVPSLVYAV QNNMAFLALS NLDAAVYQVT
YQLKIPCTAL CTVLMLNRTL SKLQWISVFM LCGGVTLVQW KPAQATKVVV AQNPLLGFGA
IAIAVLCSGF AGVYFEKVLK SSDTSLWVRN IQMYLSGIVV TLAGTYLSDG AEIQEKGFFY
GYTYYVWFVI FLASVGGLYT SVVVKYTDNI MKGFSAAAAI VLSTIASVLL FGLQITLSFA
LGALLVCVSI YLYGLPRQDT TSIQQEATSK ERIIGV
